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1.
Int J Clin Pharmacol Ther ; 47(2): 78-88, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19203563

ABSTRACT

OBJECTIVE: Recent reports have showed an antiinflammatory effect of phosphodiesterase III inhibitors (PDEi) in patients undergoing cardiopulmonary bypass (CPB). We sought to evaluate the immunological and hemodynamic response to enoximone and methylprednisolone in patients undergoing CABG. DESIGN: Prospective, randomized, controlled study. SETTING: Cardiac surgery unit in a university hospital. PATIENTS: 40 patients undergoing CPB-CABG. INTERVENTIONS: Patients receive enoximone (20, Group A) or methylprednisolone (20, Group B). MEASUREMENTS AND MAIN RESULTS: Hemodynamic response was evaluated by Swan-Ganz catheter serial measurements and perioperative Lactate and Troponin I leakage, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpah, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3), 24 hs (T4) postoperatively. Morbidity and mortality were comparable between the two groups. Group A demonstrated higher cardiac index at T2 (2.93 l/min m2 vs 2.06, p < 0.001), at T3 (3.01 vs 2.18, p < 0.001), lower indexed systemic vascular resistance at T2 (2,044 dyne s cm-5 m-2 vs 3,132, p < 0.001). Except for higher TNF-alpha in Group B at T2 (15.89 vs 22.68, p = 0.005) proinflammatory cytokines were comparable. IL-10 was higher in Group B at any postoperative time (IL-10: T1 80.74 vs 143.3, p < 0.001, T2 165.7 vs 377.4, p < 0.001, T3 203.4 vs 443.5, p < 0,001, T4 251.8 vs 437.1, p < 0.001), whereas IL-4 and IFN-gamma proved higher in Group A at all time-points (IL-4: T1 45.9 vs 31.2, p = 0.008, T2 67.2 vs 39.7, p < 0.001, T3 77.9 vs 39.2, p < 0.001, T4 102.9 vs 42.2, p < 0.001. IFN-gamma: T1 25.8 vs 15.8, p < 0.001, T2 52.2 vs 30.3, p < 0.001, T3 78.4 vs 40.8, p < 0.001, T4 159.9 vs 67.4, p < 0.001). CONCLUSIONS: Despite comparable major clinical endpoints enoximone showed a different antiinflammatory pattern compared to methylprednisolone, however, the better hemodynamic response in enoximone compared to methylprednisolone suggests enoximone as a potential antiinflammatory tool to improve the outcome in cardiac surgery.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Enoximone/pharmacology , Methylprednisolone/pharmacology , Myocardial Revascularization , Anti-Inflammatory Agents/pharmacology , Female , Hemodynamics/drug effects , Hospitals, University , Humans , Interferon-gamma/drug effects , Interferon-gamma/metabolism , Interleukins/metabolism , Male , Middle Aged , Phosphodiesterase Inhibitors/pharmacology , Postoperative Complications/prevention & control , Prospective Studies , Time Factors , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism
2.
Minerva Anestesiol ; 70(10): 739-43; 743-5, 2004 Oct.
Article in English, Italian | MEDLINE | ID: mdl-15516885

ABSTRACT

AIM: The aim of this study was to evaluate if the currently available clinical data and the time elapsing from the diagnosis to the administration of IgM and IgA-enriched immunoglobulins can predict the outcome of patients with severe sepsis and septic shock not responding to the current treatments. METHODS: All patients with these diagnoses, who did not respond to the standard treatment from August 1999 to September 2002, were retrospectively enrolled in the study. The variables evaluated included: (a) SAPS II and age at admission; (b) body temperature, mean arterial pressure, PaO2/FIO2 ratio, creatinine, blood white cell count on the day before the administration of the IgM and IgA-enriched immuno-globulins; (c) sequential organ failure assessment (SOFA) score before and during the treatment; (d) time elapsing between the diagnosis and the treatment; (e) outcome. RESULTS: Overall, 22 patients have been enrolled (17 M, 5 F, age 54.3+/-14.5 years). Eleven (50%) survived. None of the variables measured was different among survivors and nonsurvivors. Only the time elapsing from the diagnosis of severe sepsis and septic shock and the beginning of the treatment significantly differed among survivors and nonsurvivors (2.72 +/- 1.49 days vs 7.45 +/- 3.41 days respectively, p<0.005). CONCLUSION: In patients with severe sepsis and septic shock the currently available clinical variables and severity score are not valuable in identifying those patients who could take the maximal advantage from the administration of the IgM and IgA-enriched immunoglobulins. Thus, their time of administration plays a major role in the treatment of septic patients unresponding to the conventional treatment.


Subject(s)
Immunization, Passive , Immunoglobulin A/therapeutic use , Immunoglobulin M/therapeutic use , Sepsis/therapy , Shock, Septic/therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Survival Analysis
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